JP6800842B2 - プリドピジンの類似体、それらの製造および使用 - Google Patents
プリドピジンの類似体、それらの製造および使用 Download PDFInfo
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- JP6800842B2 JP6800842B2 JP2017520772A JP2017520772A JP6800842B2 JP 6800842 B2 JP6800842 B2 JP 6800842B2 JP 2017520772 A JP2017520772 A JP 2017520772A JP 2017520772 A JP2017520772 A JP 2017520772A JP 6800842 B2 JP6800842 B2 JP 6800842B2
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- Prior art keywords
- compound
- predopidine
- phenyl
- bis
- concentration
- Prior art date
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- 238000004519 manufacturing process Methods 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims description 342
- 238000000034 method Methods 0.000 claims description 223
- 229940126214 compound 3 Drugs 0.000 claims description 128
- 229940125782 compound 2 Drugs 0.000 claims description 123
- 239000000203 mixture Substances 0.000 claims description 72
- -1 3-hydroxy-3,3-bis (3- (methylthio) phenyl) propyl Chemical group 0.000 claims description 51
- 239000007800 oxidant agent Substances 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 33
- 230000008569 process Effects 0.000 claims description 26
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 18
- 150000002978 peroxides Chemical group 0.000 claims description 18
- 239000012024 dehydrating agents Substances 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
- GVZZTTUOYREDOK-UHFFFAOYSA-N 1-bromo-3-[4-(3-bromophenyl)sulfonylbutylsulfonyl]benzene Chemical compound BrC=1C=C(C=CC=1)S(=O)(=O)CCCCS(=O)(=O)C1=CC(=CC=C1)Br GVZZTTUOYREDOK-UHFFFAOYSA-N 0.000 claims description 10
- 239000001273 butane Substances 0.000 claims description 10
- XOEHHJPSIZQMJK-UHFFFAOYSA-N 1-bromo-3-[4-(3-bromophenyl)sulfanylbutylsulfanyl]benzene Chemical compound BrC=1C=C(C=CC=1)SCCCCSC1=CC(=CC=C1)Br XOEHHJPSIZQMJK-UHFFFAOYSA-N 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 9
- AQAVEFRVVVGQGC-UHFFFAOYSA-N 1-propyl-4-[3-[4-[3-(1-propyl-3,6-dihydro-2H-pyridin-4-yl)phenyl]sulfonylbutylsulfonyl]phenyl]-3,6-dihydro-2H-pyridine Chemical compound C(CC)N1CCC(=CC1)C=1C=C(C=CC=1)S(=O)(=O)CCCCS(=O)(=O)C1=CC(=CC=C1)C=1CCN(CC=1)CCC AQAVEFRVVVGQGC-UHFFFAOYSA-N 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 239000012038 nucleophile Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 claims description 6
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 claims description 5
- CURQESAXGXWBNT-UHFFFAOYSA-N 1-[3-hydroxy-3,3-bis(3-methylsulfanylphenyl)propyl]-4-(3-methylsulfanylphenyl)piperidin-4-ol Chemical compound OC(CCN1CCC(CC1)(O)C1=CC(=CC=C1)SC)(C1=CC(=CC=C1)SC)C1=CC(=CC=C1)SC CURQESAXGXWBNT-UHFFFAOYSA-N 0.000 claims description 5
- NKYFJZAKUPSUSH-UHFFFAOYSA-N 1-bromo-3-methylsulfanylbenzene Chemical compound CSC1=CC=CC(Br)=C1 NKYFJZAKUPSUSH-UHFFFAOYSA-N 0.000 claims description 5
- SLBTUZZYJLBZQV-UHFFFAOYSA-N 1-chloro-2-methylpentane Chemical compound CCCC(C)CCl SLBTUZZYJLBZQV-UHFFFAOYSA-N 0.000 claims description 5
- HNGQQUDFJDROPY-UHFFFAOYSA-N 3-bromobenzenethiol Chemical compound SC1=CC=CC(Br)=C1 HNGQQUDFJDROPY-UHFFFAOYSA-N 0.000 claims description 5
- BFFDEVPWGSZYSN-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)piperidine Chemical compound CS(=O)(=O)C1=CC=CC(C2CCNCC2)=C1 BFFDEVPWGSZYSN-UHFFFAOYSA-N 0.000 claims description 5
- FFQQQPJDBKVKDT-UHFFFAOYSA-N 4-[3-[4-(3-pyridin-4-ylphenyl)sulfonylbutylsulfonyl]phenyl]pyridine Chemical compound N1=CC=C(C=C1)C=1C=C(C=CC=1)S(=O)(=O)CCCCS(=O)(=O)C1=CC(=CC=C1)C1=CC=NC=C1 FFQQQPJDBKVKDT-UHFFFAOYSA-N 0.000 claims description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 150000002118 epoxides Chemical class 0.000 claims description 5
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 claims description 5
- FBFJNNMTTVZWIR-GJZGRUSLSA-N (1S,6S)-6-(3-methylsulfonylphenyl)-3-propyl-7-oxa-3-azabicyclo[4.1.0]heptane Chemical compound CS(=O)(=O)C=1C=C(C=CC=1)[C@]12CCN(C[C@@H]2O1)CCC FBFJNNMTTVZWIR-GJZGRUSLSA-N 0.000 claims description 4
- YDZAGNOUGPIQDK-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-propyl-3,6-dihydro-2h-pyridine Chemical compound C1N(CCC)CCC(C=2C=C(C=CC=2)S(C)(=O)=O)=C1 YDZAGNOUGPIQDK-UHFFFAOYSA-N 0.000 claims description 4
- MTJKDOUJRMHFEJ-UHFFFAOYSA-L [I-].C(CC)[N+]1=CC=CC=C1.C(CC)[N+]1=CC=CC=C1.[I-] Chemical compound [I-].C(CC)[N+]1=CC=CC=C1.C(CC)[N+]1=CC=CC=C1.[I-] MTJKDOUJRMHFEJ-UHFFFAOYSA-L 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 claims description 4
- 238000007142 ring opening reaction Methods 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- AVAYCNNAMOJZHO-UHFFFAOYSA-N [Na+].[Na+].[O-]B[O-] Chemical group [Na+].[Na+].[O-]B[O-] AVAYCNNAMOJZHO-UHFFFAOYSA-N 0.000 claims 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 132
- 239000008194 pharmaceutical composition Substances 0.000 description 128
- 229940125898 compound 5 Drugs 0.000 description 126
- 229940125904 compound 1 Drugs 0.000 description 119
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
- 239000000825 pharmaceutical preparation Substances 0.000 description 95
- 229940126534 drug product Drugs 0.000 description 86
- 239000012535 impurity Substances 0.000 description 85
- 239000000243 solution Substances 0.000 description 76
- 229940088679 drug related substance Drugs 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 239000008186 active pharmaceutical agent Substances 0.000 description 66
- 238000005259 measurement Methods 0.000 description 58
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- 239000011541 reaction mixture Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- 238000002360 preparation method Methods 0.000 description 29
- 239000012086 standard solution Substances 0.000 description 29
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- YGKUEOZJFIXDGI-UHFFFAOYSA-N pridopidine Chemical compound C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGKUEOZJFIXDGI-UHFFFAOYSA-N 0.000 description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 229950003764 pridopidine Drugs 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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- 239000003085 diluting agent Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 14
- 230000014759 maintenance of location Effects 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- WIXIJTZDQPAOPC-UHFFFAOYSA-N 4-(3-methylsulfanylphenyl)-1-propylpiperidin-4-ol;hydrochloride Chemical compound Cl.C1CN(CCC)CCC1(O)C1=CC=CC(SC)=C1 WIXIJTZDQPAOPC-UHFFFAOYSA-N 0.000 description 3
- HPGYKYONIVUKGP-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-propylpiperidin-1-ium-4-ol chloride Chemical compound [Cl-].CCC[NH+]1CCC(O)(CC1)C1=CC(=CC=C1)S(C)(=O)=O HPGYKYONIVUKGP-UHFFFAOYSA-N 0.000 description 3
- YGRHOYQMBLLGEV-UHFFFAOYSA-N 4-(3-methylsulfonylphenyl)-1-propylpiperidine;hydrochloride Chemical group Cl.C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGRHOYQMBLLGEV-UHFFFAOYSA-N 0.000 description 3
- QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 description 3
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- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical group [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 description 3
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- XIWPQKRSOBOINI-UHFFFAOYSA-N hydron 4-(3-methylsulfanylphenyl)-1-propyl-1,2,3,6-tetrahydropyridin-1-ium sulfate Chemical compound [H+].[O-]S([O-])(=O)=O.CCC[NH+]1CCC(=CC1)c1cccc(SC)c1 XIWPQKRSOBOINI-UHFFFAOYSA-N 0.000 description 2
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- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
- FNBCNCDBZZLEGS-HUUCEWRRSA-N (3S,4R)-4-(3-methylsulfonylphenyl)-1-propylpiperidin-3-ol Chemical compound CS(=O)(=O)C=1C=C(C=CC=1)[C@@H]1[C@@H](CN(CC1)CCC)O FNBCNCDBZZLEGS-HUUCEWRRSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/24—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8872—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample impurities
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Spectroscopy & Molecular Physics (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462019337P | 2014-06-30 | 2014-06-30 | |
| US62/019,337 | 2014-06-30 | ||
| US201462076436P | 2014-11-06 | 2014-11-06 | |
| US62/076,436 | 2014-11-06 | ||
| PCT/US2015/038349 WO2016003919A1 (en) | 2014-06-30 | 2015-06-29 | Analogs of pridopidine, their preparation and use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020077160A Division JP7035108B2 (ja) | 2014-06-30 | 2020-04-24 | プリドピジンの類似体、それらの製造および使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017519839A JP2017519839A (ja) | 2017-07-20 |
| JP2017519839A5 JP2017519839A5 (es) | 2018-08-09 |
| JP6800842B2 true JP6800842B2 (ja) | 2020-12-16 |
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ID=54929343
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017520772A Active JP6800842B2 (ja) | 2014-06-30 | 2015-06-29 | プリドピジンの類似体、それらの製造および使用 |
| JP2020077160A Active JP7035108B2 (ja) | 2014-06-30 | 2020-04-24 | プリドピジンの類似体、それらの製造および使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020077160A Active JP7035108B2 (ja) | 2014-06-30 | 2020-04-24 | プリドピジンの類似体、それらの製造および使用 |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US10130621B2 (es) |
| EP (2) | EP3160470B1 (es) |
| JP (2) | JP6800842B2 (es) |
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| USRE46117E1 (en) | 1999-12-22 | 2016-08-23 | Teva Pharmaceuticals International Gmbh | Modulators of dopamine neurotransmission |
| CA2810092A1 (en) | 2010-09-03 | 2012-03-08 | IVAX International GmbH | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| US9012476B2 (en) | 2011-12-08 | 2015-04-21 | IVAX International GmbH | Hydrobromide salt of pridopidine |
| UA122999C2 (uk) | 2013-06-21 | 2021-02-03 | Прайлінія Н'Юротерапьютікс Лтд. | Застосування придопідину для лікування хвороби гантінгтона |
| US11090297B2 (en) * | 2013-06-21 | 2021-08-17 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating huntington's disease |
| TW201613859A (en) | 2014-06-30 | 2016-04-16 | Teva Pharma | Analogs of PRIDOPIDINE, their preparation and use |
| CA2970799A1 (en) | 2014-12-22 | 2016-06-30 | Teva Pharmaceuticals International Gmbh | L-tartrate salt of pridopidine |
| DK3261721T3 (da) | 2015-02-25 | 2022-11-28 | Prilenia Neurotherapeutics Ltd | Anvendelse af pridopidin til forbedring af hukommelse |
| WO2023062632A1 (en) * | 2021-10-11 | 2023-04-20 | Prilenia Neurotherapeutics Ltd. | Pridopidine and analogs thereof for the treatment of neurodegenerative eye disease |
| US11471449B2 (en) | 2015-02-25 | 2022-10-18 | Prilenia Neurotherapeutics Ltd. | Use of pridopidine to improve cognitive function and for treating Alzheimer's disease |
| AR105434A1 (es) | 2015-07-22 | 2017-10-04 | Teva Pharmaceuticals Int Gmbh | Proceso para preparar pridopidina |
| EP3419622B1 (en) | 2016-02-24 | 2024-03-06 | Prilenia Neurotherapeutics Ltd. | Treatment of neurodegenerative eye disease using pridopidine |
| CN110012661A (zh) | 2016-08-24 | 2019-07-12 | 普瑞尼亚医疗发展有限公司 | 普利多匹定用于治疗肌张力障碍的用途 |
| MX2019002265A (es) | 2016-08-24 | 2019-10-30 | Prilenia Therapeutics Dev Ltd | Uso de pridopidina para el tratamiento de la disminucion funcional. |
| DK3570940T3 (da) | 2017-01-20 | 2024-02-19 | Prilenia Neurotherapeutics Ltd | Pridopidin til anvendelse i behandling af fragilt x-syndrom |
| CN116370473A (zh) | 2017-08-14 | 2023-07-04 | 普瑞尼亚神经治疗有限公司 | 用普利多匹定治疗肌萎缩性脊髓侧索硬化症的方法 |
| EP3675830A1 (en) | 2017-08-30 | 2020-07-08 | Prilenia Neurotherapeutics Ltd. | High concentration dosage forms of pridopidine |
| AU2018329628B2 (en) | 2017-09-08 | 2021-04-22 | Prilenia Neurotherapeutics Ltd. | Pridopidine for treating drug induced dyskinesias |
| JP7296472B2 (ja) * | 2019-03-15 | 2023-06-22 | プリレニア ニューロセラピューティクス リミテッド | プリドピジンを使用したミトコンドリア関連疾患および障害（それらの症状を含む）の治療 |
| EA202193190A1 (ru) * | 2019-06-12 | 2022-03-24 | Прилиния Ньюротерапьютикс Лтд. | Композиция, включающая придопидин и его аналог, для лечения болезни гентингтона и ее симптомов |
| WO2021224914A1 (en) * | 2020-05-04 | 2021-11-11 | Prilenia Neurotherapeutics Ltd. | Treatment of viral infection, disease or disorder using a selective s1r agonist |
| CN116472043A (zh) * | 2020-10-20 | 2023-07-21 | 普瑞尼亚神经治疗有限公司 | 普利多匹定和类似物用于治疗焦虑和抑郁的用途 |
| CA3192542A1 (en) * | 2020-10-20 | 2022-04-28 | Michael Hayden | Use of pridopidine and analogs for the treatment of anxiety and depression |
| IL307462A (en) * | 2021-04-14 | 2023-12-01 | Prilenia Neurotherapeutics Ltd | Treatment of Huntington's disease in a prodromal state |
| CN114716391B (zh) * | 2022-04-24 | 2023-12-12 | 杭州仟源保灵药业有限公司 | 一种醋甲唑胺杂质及其制备方法和应用 |
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| KR20060117355A (ko) * | 2004-01-21 | 2006-11-16 | 테바 파마슈티컬 인더스트리즈 리미티드 | 발라시클로버 염산염의 제조 방법 |
| JP2008501748A (ja) * | 2004-06-08 | 2008-01-24 | ニューロサーチ スウェーデン アクチボラゲット | ドーパミン神経伝達のモジュレーターとしての新規な置換されたピペリジン |
| SE0401465D0 (sv) * | 2004-06-08 | 2004-06-08 | Carlsson A Research Ab | New substituted piperdines as modulators of dopamine neurotransmission |
| WO2006029253A2 (en) * | 2004-09-04 | 2006-03-16 | Teva Pharmaceutical Industries Ltd. | A valacyclovir impurity, process for the preparation of valacyclovir impurity and use as a reference standard |
| EP1807394A1 (en) * | 2004-10-13 | 2007-07-18 | Neurosearch Sweden AB | Process for the synthesis of 4-(3-sulfonylphenyl)-piperidines |
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| CN101765428A (zh) * | 2007-06-18 | 2010-06-30 | A·卡尔森研究股份有限公司 | 多巴胺稳定剂的用途 |
| US20110206782A1 (en) * | 2010-02-24 | 2011-08-25 | Auspex Pharmaceuticals, Inc. | Piperidine modulators of dopamine receptor |
| CN103080343A (zh) | 2010-07-02 | 2013-05-01 | Skf公司 | 机械部件和用于表面硬化的方法 |
| CA2810092A1 (en) | 2010-09-03 | 2012-03-08 | IVAX International GmbH | Deuterated analogs of pridopidine useful as dopaminergic stabilizers |
| US9006445B2 (en) | 2011-09-07 | 2015-04-14 | IVAX International GmbH | Polymorphic form of pridopidine hydrochloride |
| US9012476B2 (en) | 2011-12-08 | 2015-04-21 | IVAX International GmbH | Hydrobromide salt of pridopidine |
| CA2869145A1 (en) | 2012-04-04 | 2013-10-10 | IVAX International GmbH | Pharmaceutical compositions for combination therapy |
| US20150216850A1 (en) | 2012-09-27 | 2015-08-06 | Michael Hayden | Combination of rasagiline and pridopidine for treating neurodegenerative disorders, in particular huntington's disease |
| WO2014052933A1 (en) | 2012-09-27 | 2014-04-03 | Teva Pharmaceutical Industries Ltd. | Laquinimod and pridopidine for treating neurodegenerative disorders |
| UA122999C2 (uk) | 2013-06-21 | 2021-02-03 | Прайлінія Н'Юротерапьютікс Лтд. | Застосування придопідину для лікування хвороби гантінгтона |
| US20150202302A1 (en) | 2014-01-22 | 2015-07-23 | IVAX International GmbH | Modified release formulations of pridopidine |
| TW201613859A (en) | 2014-06-30 | 2016-04-16 | Teva Pharma | Analogs of PRIDOPIDINE, their preparation and use |
| CA2970799A1 (en) | 2014-12-22 | 2016-06-30 | Teva Pharmaceuticals International Gmbh | L-tartrate salt of pridopidine |
| DK3261721T3 (da) | 2015-02-25 | 2022-11-28 | Prilenia Neurotherapeutics Ltd | Anvendelse af pridopidin til forbedring af hukommelse |
| WO2016138135A1 (en) | 2015-02-25 | 2016-09-01 | Teva Pharmaceuticals International Gmbh | Sigma-1 receptor modulators for treating huntington's disease |
| AR105434A1 (es) | 2015-07-22 | 2017-10-04 | Teva Pharmaceuticals Int Gmbh | Proceso para preparar pridopidina |
| US20170020854A1 (en) | 2015-07-22 | 2017-01-26 | Teva Pharmaceuticals International Gmbh | Pridopidine base formulations and their use |
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